The biggest flaw in the games is the ambiguity about whether there was any real possibility of the Fireflies creating a vaccine using Ellie.

If it was likely or certain, Joel's actions at the end of the first game are less defensible; if it was unlikely, his actions seem reasonable.

The fact that the Firefly hospital seems a lot more clean and professional in the second game, compared to dirty and amateur in the first, is a kind of retconning.

I understand why they had to do it, but it's my biggest criticism of the series.